Numerous studies have demonstrated that both the risk of coronary heart disease (CHD) in humans and the severity of experimental atherosclerosis in animals are inversely correlated with serum HDL cholesterol (HDL-C) concentrations (Russ et al, Am. J. Med., 11 (1951) 480-493; Gofman et al, Circulation, 34 (1966) 679-697; Miller and Miller, Lancet, 1 (1975) 16-19; Gordon et al, Circulation, 79 (1989) 8-15; Stampfer et al, N. Engl. J. Med., 325 (1991) 373-381; Badimon et al, Lab. Invest., 60 (1989) 455-461 ). Atherosclerosis is the process of accumulation of cholesterol within the arterial wall which results in the occlusion, or stenosis, of coronary and cerebral arterial vessels and subsequent myocardial infarction and stroke. Angiographical studies have shown that elevated level of some HDL particles in humans appears to be correlated to a decreased number of sites of stenosis in the coronary arteries of humans (Miller et al, Br. Med. J., 282 (1981) 1741-1744).
There are several mechanisms by which HDL may protect against the progression of atherosclerosis. Studies in vitro have shown that HDL is capable of removing cholesterol from cells (Picardo et al, Arteriosclerosis, 6 (1986) 434-441). Data of this nature suggest that one antiatherogenic property of HDL may lie in its ability to deplete tissues of excess free cholesterol and eventually lead to the delivery of this cholesterol to the liver (Glomset, J. Lipid Res., 9 (1968) 155-167). This has been supported by experiments showing efficient transfer of cholesterol from HDL to the liver (Glass et al, Circulation, 66 (Suppl. I) (1982) 102; MacKinnon et al, J. Biol. Chem., 261 (1986) 2548-2552). In addition, HDL may serve as a reservoir in the circulation for apoproteins necessary for the rapid metabolism of triglyceride-rich lipoproteins (Grow and Fried, J. Biol. Chem., 253 (1978) 1834-1841; Lagocki and Scanu, J. Biol. Chem., 255 (1980) 3701-3706; Schaefer et al, J. Lipid Res., 23 (1982) 1259-1273). Accordingly, agents which increase HDL cholesterol concentrations are useful as anti-atherosclerotic agents, particularly in the treatment of dyslipoproteinemias and coronary heart disease.
U.S. Pat. No. 5,411,981 discloses N-phenyl imidazolidines of the following formula (I) as anti-androgenic agents useful in the treatment of cancers of the breast, brain, ovaries, bladder, liver and kidney: ##STR2## in which --A--B-- is ##STR3## where R.sup.1 is cyano, nitro or halogen; R.sup.2 is trifluoromethyl or halogen; X is oxygen or sulfur; Y is oxygen, sulfur or nitrogen and R.sup.3 is hydrogen or a vast variety of organic groups.
Related publication EP 5785 16 emphasizes compounds of formula Ia, with special emphasis on the 4-cyano-2-trifluoromethyl-phenyl group in each of the disclosed species.
WO 94/20460 discloses a genus of compounds of formula II as angiotensin-II receptor antagonists, useful for the treatment of hypertension, congestive heart failure, renal failure and glaucoma. ##STR4##
In the generic disclosure, HET represents numerous heterocycles, one of which is an imidazolidinone (III) in which R2 may be an 2-8 C alkylthio group among other things. There is no specific example of a compound disclosed in the document that corresponds with those variables. R.sup.22 is a 3-4 membered polymethylene (spiro) group.